Title

Author

Date Approved

2009

Degree Type

Open Access Thesis

Degree Name

Master of Science (MS)

Department

Chemistry

Committee Member

Dr. Deborah Heyl-Clegg, PhD, Chair

Abstract

Amylin (Islet Amyloid Polypeptide, IAPP) is a 37 amino acid polypeptide, co-secreted with insulin from pancreatic beta cells, that plays a role in the damage of cell membranes by forming amyloid fibrils in Type 2 diabetes. Insulin has been found to inhibit hIAPP (Human Islet Amyloid Polypeptide) aggregation. The HLVEALYLVC amino acid region of insulin contacts hIAPP near the N-terminus. Truncated and modified analogs of insulin containing the binding region (VEALYLV, VEALFLV and EALYLV) were synthesized and purified, and their actions were studied on model lipid membranes in the presence of hIAPP 1-19 and hIAPP 1-37.

Comments

Results indicate that the presence of the aromatic hydroxyl group on tyrosine is not a requirement for activity and may be detrimental to the interaction with hIAPP. The analogs were found to be ineffective against the actions of hIAPP 1-37 and were found to show similar actions to insulin itself. In addition, at high molar ratios of inhibitor to hIAPP 1-37, they were found to promote membrane damage. However, VEALYLV was found to be effective in reducing the dye leakage caused by hIAPP 1-19 at higher molar ratios. This implies that the small inhibitors may block initial damage caused by the N-terminus of hIAPP but are unable to stop fiber formation mediated by the C-terminal region.